The invention generally relates to the field of nuclear magnetic resonance (NMR), and relates in particular to magnetic resonance imaging (MRI).
MRI systems generally provide for diagnostic imaging of regions within a subject by detecting the precession of the magnetic moments of atomic nuclei in an applied external magnetic field. Spatial selectivity, allowing imaging, is achieved by matching the frequency of an applied radio-frequency (rf) oscillating field to the precession frequency of the nuclei in a quasi-static field. By introducing controlled gradients in the quasi-static applied field, specific slices of the subject can be selectively brought into resonance. By a variety of methods of controlling these gradients in multiple directions, as well as controlling the pulsed application of the rf resonant fields, three-dimensional images representing various properties of the nuclear precession can be detected, giving information about the density of nuclei, their environment, and their relaxation processes. By appropriate choice of the magnitude of the applied quasi-static field and the rf frequency, different nuclei can be imaged. Typically, in medical applications of MRI, it is the nuclei of hydrogen atoms, i.e., protons, that are imaged. This is, of course, not the only possibility. Information about the environment surrounding the nuclei of interest can be obtained by monitoring the relaxation process whereby the precessional motion of the nuclei is damped, either by the relaxation of the nuclear moment orientation returning to alignment with the quasi-static field following a tipping pulse (on a time scale T1), or by the dephasing of the precession due to environmental effects that cause more or less rapid precession, relative to the applied rf frequency (on a time scale T2).
Conventional MRI contrast agents, such as those based on gadolinium compounds, operate by locally altering the T1 or T2 relaxation processes of protons. Typically, this relies on the magnetic properties of the contrast agent, which alters the local magnetic environment of protons. In this case, when images display either of these relaxation times as a function of position in the subject, the location of the contrast agent shows up in the image, providing diagnostic information.
An alternative approach to MRI imaging is to introduce into the subject an imaging agent, the nuclei of which themselves are imaged by the techniques described above. That is, rather than affecting the local environment of the protons in the body and thereby providing contrast in a proton image, the imaging agent is itself imaged. Such imaging agents include substances that have non-zero nuclear spin such as 3He, 129Xe, 31P, 29Si, 13C and others. The nuclei in these substances may be polarized by various methods (including optically or using sizable applied magnetic fields at room or low temperature), orienting a significant fraction of the nuclei in the agent (hyperpolarizing), before introduction into the body, and then introducing the polarized material into the body. Once in the body, a strong imaging signal is obtained due to the high degree of polarization of the imaging agent. Also there is only a small background signal from the body, as the imaging agent has a resonant frequency that does not excite protons in the body. For example, U.S. Pat. No. 5,545,396 discloses the use of hyperpolarized noble gases for MRI.
Many proposed agents for hyperpolarized MRI have short relaxation (T1) times, requiring that the material be quickly transferred from the hyperpolarizing apparatus to the body, and imaged very soon after introduction into the body, often on the time scale of tens of seconds. For a number of applications, it is desirable to use an imaging agent with longer T1 times. For example, U.S. Pat. No. 6,453,188 discloses a method of providing magnetic resonance imaging using a hyperpolarized gas that provides a T1 time of several minutes and possibly up to sixteen minutes (1000s). Compared to gases, solid—or liquid materials usually lose their hyperpolarization rapidly. Hyperpolarized substances are, therefore, typically used as gases. Protecting even the hyperpolarized gas from losing its magnetic orientation, however, is also difficult in certain applications. For example, U.S. Published Patent Application No. 2003/0009126 discloses the use of a specialized container for collecting and transporting 3He and 129Xe gas while minimizing contact induced spin relaxation. U.S. Pat. No. 6,488,910 discloses providing 129Xe gas or 3He gas in microbubbles that are then introduced into the body. The gas is provided in the microbubbles for the purpose of increasing the T1 time of the gas. The relaxation time of such gas, however, is still limited.
U.S. Published Patent Application No. 2004/0024307 discloses the use of para-hydrogen labeled imaging agents using non-zero nuclear spin atoms such as 13C, 15N, 29Si, 19F, 3Li, 1H, and 31P in a host molecule using enriched hydrogen. The hydrogenated imaging agent is then employed in a soluble form in a liquid or solvent for MRI and is disclosed to have a T1 time of preferably about 1000 s or longer.
U.S. Published Patent Application No. 2005/0136002 discloses the use of a particulate contrast agent that includes non-zero nuclear spin atoms such as 19F, 13C, 15N, 29Si, 31P, 129Xe and 3He. The particulate composition is disclosed to respond to physiological conditions in a subject to provide improved imaging by changing contrast characteristics. The responses to physiological conditions are disclosed to include melting, or changing the viscosity or chemical composition of the subject. The spin relaxation times, however, are generally disclosed to be less than 1 s.
There is a need, therefore, for a contrast agent or imaging agent that provides greater flexibility in designing relaxation times during nuclear magnetic resonance imaging.